The causal relationship between cheese intake and atherosclerosis: A two-sample mendelian randomization study

Abstract Background Previous observational studies have yielded conflicting results regarding the association between cheese intake and atherosclerosis, and the relative contribution to each subtype (coronary atherosclerosis, peripheral atherosclerosis, cerebral atherosclerosis and arterial stiffness) remains unclear. We sought to systematically investigate the causal link between cheese intake and atherosclerosis. Methods A two-sample MR study was conducted to investigate the causal relationship between cheese intake and atherosclerosis subtypes. Summary statistics from genome-wide associations of cheese intake (N= 451,486 individuals), coronary atherosclerosis (N= 14,334 cases, 346,860 controls), peripheral atherosclerosis (N= 6,631 cases, 162,201 controls), arterial stiffness (N= 151,053 individuals, no available cases/controls), cerebral atherosclerosis (N= 104 cases, 218,688 controls), and atherosclerosis (excluding cerebral, coronary and PAD) (N= 6,599 cases, 212,193 controls) were used in the MR study. Inverse variance weighted (IVW) analysis was utilized for the study's main result, and weighted median, MR Egger, and weighted mode analyses were used as complementary analyses to IVW. Moreover, the results were robustly examined through a sensitivity analysis. Results Genetically predicted cheese intake was positively associated with coronary atherosclerosis (OR=0.98, 95%CI=0.97–0.99, P=0.002), peripheral atherosclerosis (OR=0.56, 95%CI=0.37–0.84, P=0.006), arterial stiffness (OR=0.87, 95%CI=0.81–0.94, P=0.001), and atherosclerosis (excluding cerebral, coronary and PAD) (OR=0.65, 95%CI=0.43–0.98, P=0.037) in the inverse variance weighted analysis. However, no causal relationship between cheese intake and cerebral atherosclerosis was observed (OR=0.91, 95%CI=0.07–11.28, P=0.941). Conclusion Our two-sample MR analysis revealed that cheese intake was significantly associated with an increased risk of coronary atherosclerosis, peripheral atherosclerosis, arterial stiffness, and atherosclerosis (excluding cerebral, coronary and PAD). However, no causal relationship between cheese intake and cerebral atherosclerosis was observed in the MR analysis.